Murray Sheldon, MD Associate Director for Technology and Innovation Center for Devices and Radiological Health (CDRH) Office of the Center Director The National Academies Innovation Policy Forum September 10, 2014
It s About the Patients
FDA & US Medical Device Innovation CDRH Mission Facilitate medical device innovation by providing industry with predictable, consistent, transparent and efficient regulatory pathways Provide stakeholders with understandable and accessible science-based information about medical devices CDRH Vision Patients in the US have access to high-quality, safe, and effective medical devices of public health importance first in the world US is the world s leader in medical device innovation 3
Makower Report (2010): FDA Impact on US Medical Technology Innovation United States Same starting point: Clinical Development Europe Apply for IDE 0 7 $10M $8M $40M $13M Safety study $8M $1M Safety study Initial reimbursement CE mark approval CE mark submission Pivotal study FDA submission FDA approval Initial reimbursement 14 21 28 35 42 49 56 63 70 (months) ~ 4 years longer to regulatory approval in US versus Europe Adapted from: Josh Makower white paper, FDA Impact on US Medical Technology Innovation, November 2010 4
U.S. Medical Device Manufacturing Companies by Number of Employees 5% 2% 10% 14% 69% Number of Employees <10 10 to 19 20 to 99 100 to 499 >500 Source: Dun and Bradstreet, Inc.
$US (Billion) The Crisis in Medical Device Innovation Start-Up investment down >35% since 2007 peak 4 3.5 3 2.5 2 1.5 1 0.5 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 6
US Medical Device Industry: Innovation Challenges Factors cited as having the highest impact on decisions to move medical device investment outside of U.S.* Regulatory Challenges 38% Reimbursement Concerns 18% Clinical Trial Issues 14% * from National Venture Capital Association/Medical Innovation & Competitiveness Coalition survey of 259 NVCA member firms investing in the healthcare sectors; 60% (156 firms responding) October, 2011 7
Time is Money Versant Ventures 8
US Medical Device Development: Current Landscape FDA acknowledges real or perceived issues: Early clinical study of novel devices moved/moving OUS Device innovation may follow OUS Devices are being exclusively developed for non-us markets FDA s requirements can be an impediment to timely clinical study of novel early-stage devices Growing concern regarding the time lag in the availability of beneficial medical devices for US patients 9
Case Study: Trans-Aortic Valve Replacement (TAVR) Initial devices were developed by start-up companies outside of U.S. It was 9 years from first-in-man (in France) to US regulatory approval It took 4 years from CE Mark to FDA approval U.S. was the 43 rd country in the world to receive approval (Brazil 42 nd, Albania 44 th ) 20-30,000 patients received TAVR worldwide before US approval Edwards and Medtronic have spent ~ $2 Billion combined bringing devices to US market 10
Climate Change at FDA How can the FDA innovate itself? How can the FDA spur innovation in the regulated industry? What is FDA s role in strengthening the U.S. Medical Device Ecosystem? 11
Climate Change at FDA FDA recognizes: A need for a cultural change to emphasize the role of promoting public health while maintaining our standards in protecting public health Human costs associated with delaying access to new technology, in the context of the limitations of current treatment alternatives Advantages for the device development process with US clinical studies (including FIH and early feasibility studies) Opportunity for close contact between developers and investigators Early access to promising novel technology
Words into Deeds The core principles in meeting these priorities are the application of specific guidelines throughout the regulatory decision-making process: Benefit/Risk Principles Identifies the factors to make benefit/risk determinations during premarket review Early Feasibility Studies Application of benefit/risk principles to justify study initiation The Innovation Pathway Pilot program for innovative devices with promising and potentially far reaching benefits CDRH 2014-2015 Strategic Priorities http://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cdrh/cdrhinnovation/innovationpathway/default.htm
Benefit-Risk Principles Allow regulators to: Consider the totality of the benefit/risk profile for the device, for example: Disease condition (e.g., life-limiting, life-threatening) Limitations of and risks associated with currently available therapies Consider patient tolerance for risk and perspective on benefits Severity and chronicity of disease Availability of alternative treatments/diagnostic modalities Take into account risk mitigation strategies when balancing risks and benefits http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm267829.htm
Early Feasibility Studies Intended to facilitate the earliest clinical evaluation of medical devices in the US under the Investigational Device Exemptions (IDE) regulations Elements that define an early feasibility study: Device intended for a specific indication that may be early in development, typically before the device design has been finalized When exhaustive nonclinical testing would not likely provide the information needed to further device development Small number of subjects mitigate risks EFS IDE approval may be based on less non-clinical data 15 http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm279103.pdf
The Innovation Pathway Pilot program launched February 2011 Targeted for pioneering technologies that address unmet clinical needs and have the potential to revolutionize patient care or health care delivery Breakthrough technology that provides a clinically meaningful advantage over existing technology No approved alternative treatment or means of diagnosis exists Significant, clinically meaningful advantages over existing approved alternative treatments
1) When the goals are understood, the methods to achieve them can be improvised. 2) We value improvisation, experimentation, risktaking, and problem-solving over process-following and standardization (uniformity of approach). 3) Okay to fail. Edison: Hell, we ain t got no rules around here. We re trying to accomplish something! 17
Innovation Program Goals Shorten the time from concept to commercialization Early and continuous interaction between FDA and sponsors to facilitate innovation; apply B/R principles Transform the user experience Create shared one team view of success Collaboration is the key Make decisions that create forward momentum Understand costs (time) of different regulatory choices Trade-offs; uncertainty; mitigations 18
32 Device applicants; 3 selected Collaboration Phase Summer 2012 HemoAccess Valve System A mechanical valve system allowing blood flow into AV graft only during dialysis Wearable Artificial Kidney A miniaturized wearable dialysis machine to provide hemodialysis Implantable Bio-Artificial Kidney (Univ. California, San Francisco) Filters toxins from blood, and provide other biological functions giving patients 24/7 dialysis 19
ENTRPRENEURS-IN-RESIDENCE (EIR) PROGRAM Goal: Transformational change by combining the internal and external talent applying lean engineering and Innovation Pathway principles Supported by the White House Office of Science and Technology Policy EIR 2011-2012 Time-limited recruitment of world-class innovators entrepreneurs and visionaries from a variety of medical-device related fields to join highly-qualified FDA staff in the development of solutions in areas that impact innovation 20
Entrepreneurs in Residence 2012-2013 Three New Projects (EIR groups): Streamlining clinical trials: Find ways to reduce the time and cost of clinical trials in support of FDA approval or clearance of medical devices Striking the right balance between pre- and postmarket evidentiary requirements: Find ways to allow efficient use of pre-market studies to allow for timely approvals, with greater emphasis on capturing informative real-world data in postmarket studies Streamlining approval to reimbursement: Find ways to reduce the inefficiencies and delays in data collection to support FDA approval and CMS coverage 21
http://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cdrh/cdrhvisionandmission/ucm384576.pdf CDRH 2014-2015 STRATEGIC PRIORITIES Strengthen the Clinical Trial Enterprise in the US Strike the Right Balance Between Premarket and Postmarket Data Collection 22 Provide Excellent Customer Service
Strengthen the Clinical Trial Enterprise IDE CYCLES Reduce the number of IDEs requiring more than two cycles to an appropriate full approval decision Sept. 30, 2014 25%* June 30, 2015 50%* IDE APPROVAL TIME Reduce the overall median time to appropriate full IDE approval by Sept. 30, 2014-25%* Increase the number of early feasibility/fih IDE studies submitted to FDA and conducted in the U.S. Clinical Trials Program Implemented FDASIA Benefit-Risk Determinations *Compared to FY 2013 performance
DAYS 500 400 300 200 100 Strengthen the Clinical Trial Enterprise CDRH FY 2015 Target: Reduce overall median time to full appropriate IDE approval to 30 days 0 FY 2011 FY 2013 FY 2015 Median Time to Full Appropriate IDE Approval 24
Strike the Right Balance Between Premarket and Postmarket Data Collection Assure the appropriate balance between pre- and postmarket data requirements to facilitate and expedite the development and review of medical devices Device types subject to a PMA that have been on the market: By12/31/14 review 50% By 6/30/15 review 75% By 12/31/15 review 100% to determine whether or not to shift some premarket data requirements to the postmarket setting or to pursue down classification, and communicate those decisions to the public Develop and seek public comment on a new pathway to market for devices subject to a PMA that address an unmet public health need by shifting appropriate premarket data needs to the postmarket setting and incorporating features of the Innovation Pathway pilots Develop and seek public comment on a framework for when it is appropriate to shift premarket data collection to the postmarket setting
National Medical Device Postmarket Surveillance Plan
Provide Excellent Customer Service Implement Customer Service Standards Assess customer satisfaction using a standardized survey tools By 12/31/14, achieve at least 70 percent customer satisfaction. By 6/30/15, achieve at least 80 percent customer satisfaction. By 6/31/15, achieve at least 90 percent customer satisfaction. Implement the principles and practices outlined in the CDRH Quality Management Framework to improve the quality and performance of CDRH processes and services.
Keys to Patient Access Evidence Value Reimbursement Market
Medical Device Reimbursement Task Force Winning coverage and payment has become a steeper challenge than gaining FDA approval for small device firms in recent years Mike Carusi on behalf of NVCA, AdvaMed and MDMA Mission Streamline the pathway from regulatory clearance or approval to reimbursement to support patient access to innovative medical devices Plan Develop a voluntary process that facilitates earlier interactions with payers, including private 3 rd party payers about evidence to support coverage and reimbursement Staff OCD / ODE / OIR with support from CMS 29
What are we proposing? FDA Review Team Manufacturer Payer Provide a process to enable manufacturers to include and engage payers during meetings with FDA using the Pre-Submission program. 30
Looking to the Future Based on Innovation Pathway pilots Focus is to expedite patient assess for: High risk medical devices Treatment or diagnosis of a life-threatening or irreversibly debilitating disease or condition Addresses an unmet medical need that Has no alternative treatment or means of diagnosis Represents breakthrough technology Provides a clinically meaningful advantage over existing technology Draft guidance issued April 23, 2014 http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm393879.htm 31
Looking to the Future Based on 2014-15 Strategic Priority #2 Supports expedited patient access pathway for PMA devices Determined by Benefit-Risk Profile Supported by FD&C Act, section 513(a)(3)(c) Allows for approval with greater degree of uncertainty for devices that serve an unmet need Supported by the National Medical Device Postmarket Surveillance system Draft guidance issued April 23, 2014 http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm393882.htm 32